• Insulin sensitivity [ Time Frame: Measured at Week 26 ] [ Designated as safety issue: No ]
• Visceral fat mass [ Time Frame: Measured at Week 26 ] [ Designated as safety issue: No ]
• Total adiposity [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]

• Measured at Week 26: Insulin sensitivity
• Visceral fat mass
• Total adiposity

• Body mass index [ Time Frame: Measured at Week 26 ] [ Designated as safety issue: No ]
• Fasting glucose [ Time Frame: Measured at Week 26 ] [ Designated as safety issue: No ]
• Fasting lipids [ Time Frame: Measured at Week 26 ] [ Designated as safety issue: No ]
• Fasting insulin [ Time Frame: Measured at Week 26 ] [ Designated as safety issue: No ]
• Total psychiatric hospital days [ Time Frame: Measured at Week 26 ] [ Designated as safety issue: Yes ]

• Measured at Week 26: Body mass index
• Fasting glucose
• Fasting lipids
• Fasting insulin

This study will evaluate the effectiveness of ziprasidone treatment versus treatment with a standard atypical antipsychotic drug in improving insulin sensitivity and reducing excess abdominal fat storage in people with schizophrenia who are at risk for diabetes.

People with schizophrenia often lead more sedentary lifestyles than people without the disease, and they are frequently treated with antipsychotic medications that cause weight gain. Combined, these factors produce an increased risk for metabolic syndrome, which can lead to heart disease and type 2 diabetes. Characteristics of metabolic syndrome include carrying excess weight around the abdominal region; high blood pressure; high blood sugar levels; high levels of fat in the blood; and low levels of HDL cholesterol. Recent studies have shown that certain atypical antipsychotic drugs are relatively weight-neutral. Switching from a drug that promotes weight gain to a weight-neutral medication, such as ziprasidone, may result in significant weight loss. There is insufficient evidence, however, demonstrating the extent of improvement in insulin sensitivity after switching medications. This study will evaluate the effectiveness of ziprasidone treatment versus treatment with a standard atypical antipsychotic drug in improving insulin sensitivity and reducing excess abdominal fat storage in people with schizophrenia who are at risk for diabetes.

Participants in this open label study will currently be undergoing treatment with risperidone or olanzapine at the time of study entry. Upon study entry, they will be randomly assigned to either switch to ziprasidone treatment or remain on their current medications. Both groups will be treated for 26 weeks. Participants will report to the study site for evaluations biweekly until week 10 and then monthly for the duration of the study. The following outcomes will be assessed at study entry and Week 26: insulin sensitivity, using an intravenous glucose tolerance test; visceral fat mass, using a CT scan; and total adiposity, using a dexascan.

• Schizophrenia
• Metabolic Syndrome X
• Insulin Resistance

• Drug: Ziprasidone
• Drug: Standard atypical antipsychotic drug

• Active Comparator: Participants on risperidone or olanzapine who will remain on risperidone or olanzapine and do not switch to ziprasidone
• Experimental: Participants who enter on risperidone or olanzapine and switch to ziprasidone

Inclusion Criteria:

• Diagnosis of schizophrenia or schizoaffective disorder
• Currently receiving antipsychotic therapy with risperidone or olanzapine
• Overweight

Exclusion Criteria:

• Diagnosis of diabetes
• Hospitalization for schizophrenia or schizoaffective disorder within 90 days prior to study entry
• Refractory schizophrenia or schizoaffective disorder
• Currently receiving therapy with clozapine
• No stable residence and phone number for 90 days prior to study entry
• Prior unsuccessful treatment with ziprasidone
• Intolerance to ziprasidone